The alveoli of the lung are composed of a delicate web of endothelial and epithelial cells which interface between the environment and the blood stream. As part of maintenance and response to injury, these structures must undergo constant repair. Repair and maintenance of adult alveoli is not well understood. The hypothesis tested in this application is that endothelial and epithelial alveolar progenitor cells can be identified in dissociated and young adult lungs by a composite phenotype of surface markers, and this phenotype can be used to isolate these cells. We further hypothesize that these cells, when infused into recipients that have undergone lung injury, will participate and augment alveolar repair. Our preliminary data suggest that using such an approach, we have isolated a population of lung cells, that when infused into lethally irradiated recipients by intravenous injection, appears to be enriched for endothelial progenitor cell (EPC) activity demonstrated by participation in regeneration of alveolar capillaries. Our observation that donor cells can participate in the generation of endothelial clusters in lung, is a novel finding. We have additionally determined that introduction of dissociated lung populations by direct intratracheal route results in successful dispersion of the cells throughout the lung of recipients and observed cells in alveoli which appear to be of epithelial origin. The research proposed in this R21 will aim to further purify and characterize the putative alveolar EPCs, and determine if alveolar epithelial progenitor cells (AepPc) can be similarly isolated and participate in lung repair. The studies proposed in this application address issues of both basic understanding of adult lung stem cell biology and the potential use of purified lung progenitors for organ repair. If successful the populations identified in these studies may be used as therapy for acute lung injury such as acute respiratory distress syndrome (ARDS), radiation pneumonitis, and chemotherapy induced lung injury. [unreadable] [unreadable] [unreadable]